Intrathecal

Intrathecal morphinics reinforce intraoperative analgesia and participate in postoperative analgesia. Other molecules, such as neostigmine, have been tested as adjuvants to local anesthetics for a better postoperative analgesia. The superiority of neostigmine over morphine administered intrathecally has not been proven. We propose to compare the effectiveness of postoperative analgesia provided by100 μg Intrathecal morphine to that of 25 μg of neostigmine during spinal anaesthesia in patients proposed for femur surgery. Show that the management of postoperative pain can be done with safe adjuvants. This was a prospective and analytical study over a three-month period from September 1 to November 30, 2019. There were sixty randomized double-blind male patients divided into two groups: Group M: received a mixture of 15 mg bupivacaine 0.5% isobaric acid μg fentanyl + 100 μg morphine. Group N: received a mixture of 15 mg bupivacaine 0.5% isobaric acid + 25 μg fentanyl + 25 μg neostigmine. The variables studied were demographic, hemodynamic, postoperative pain, adverse effects, quality of sensory and motor block. The analysis was done using the SPSS 10.0 software. The Ki-2 test was used to compare the qualitative variables and the student t test for the quantitative ones. The significance threshold was set at 5%. During the study period 401 patients were operated on. General anaesthesia was performed in 63.34% of cases and rachianesthesia in 36.50%. The mean age was 30 ± 6 years in the N group and 32 ± 4 years in the M. The ASA class was comparable in both groups. Arterial hypertension was the main antecedent (13.3% for the N group versus 20% for the M.). The average duration of the procedure was 90 ± 8 minutes. At the exit of the operating room the EVA score was nil in all patients. At the first postoperative hour the EVA score was 08 ± 3 mm in the N group versus 06 ± 3 mm in the M group (p = 0.852). At the fourth postoperative hour the EVA score was 15.6 ± 20 mm in the N group versus 3.3 ± 8 mm in the M (p = 0.003). But at the eighth postoperative hour in the N group the EVA score was 33.6 ± 33 mm versus 4 ± 9 mm; the difference was statistically significant (p ˂ 0.001). On the other hand, in group M, the acme of pain was observed only at the 24th hour. In group N, the use of supplemental intravenous morphine analgesia during the first 24 postoperative hours was observed in 16 patients (533%), whereas no additional analgesia was considered necessary in the M. The difference was significant (p ˂ 0.001). The average intravenous morphine consumption in the N group was 2.6 ± 1 mg with extremes of 2 to 4 mg. The average interval of the first request for additional analgesia was 3 hours with extremes of 1 to 8 hours. In group N, 56.7% of patients had nausea and vomiting compared to 16.7% in group M, the difference was significant (p = 0.0001). We recorded 23.3% of the pruritic cases in the N group versus 33.3% in the M group, the difference was not significant (P = 0.39). Intrathecal neostigmine at a dose of 25 μg provides less postoperative analgesia than intrathecal morphine 100 μg. Intrathecal neostigmine remains limited because of the high incidence of nausea and vomiting.

Intrathecal baclofen is the reference treatment for severe spasticity. This drug has to be injected chronically in the intrathecal space by
implanted pumps which are very expensive, uncomfortable and sometimes lead to side effects. Previous work has been performed by our
group to assess the feasibility of encapsulating baclofen into poly(lactide-co-glycolide) (PLGA) microspheres and injecting these
preparations in the intrathecal space of rabbits. The aims of the present study were to improve the encapsulation process for industrial
application (scale-up), and to set up an animal model to assess the duration of effect of the new formulations. Modifications included the
replacement of methylene chloride by a less toxic solvent, ethyl acetate, and the use of high molecular weight polymers to extend the release
rate of the drug. The temperature and organic solvent extraction rate were fully controlled during the whole manufacturing process. All these
modifications resulted in high quality microsphere batches with a CV inferior to 5% for encapsulation efficiency and drug loading.
Encapsulation efficiency and release patterns were dependent on the drug payload and the polymer used. A formulation displaying a
sustained release of baclofen over 174 days and a moderate burst effect of 16% in the first day in vitro was evaluated in a new reliable model
of baclofen activity based on electrophysiological measurement of H-reflex in the rabbit. The activity of a very low dose of baclofen
microspheres in vivo was sustained over 35 days. Furthermore, the preparation was well tolerated. These newly developed preparations are a
very promising approach for enhancing the efficacy and comfort of patients undergoing spasticity treatment.